We are continuing to work on several aspects of the distal tubule-glomerular feedback mechanism and are currently conducting experiments which will provide greater insight into the mechanism for the transmission of feedback signals between distal tubular lumen and the vascular effector system. Previously, we found that the first step in the initiation of feedback signals involved the detection of changes in luminal fluid osmolality. The cellular mechanism whereby the macula densa cells detect changes in luminal fluid osmolality remains unknown. One possibility is an alteration in the cytoplasmic calcium (Ca ions) concentration. We have now conducted retrograde microperfusion studies in rats assessing the effects of elevations in intracellular Ca ions on the magnitude of stop flow pressure feedback responses. Cytoplasmic Ca ions were increased by the use of the Ca ions ionophore A23187. In the presence of high intraluminal Ca ions, maximal feedback responses were obtained even in the absence of a luminal osmotic stimulus. These results tentatively suggest that alterations in cytoplasic Ca ions may serve as intermediary steps in the transmission of feedback signals. We plan to continue these studies including assessing the effects of removal of Ca ions from the luminal solution, the effects of diuretics on Ca ions-mediated responses and determining whether the cytoplasmic Ca ions system is necessary for the transmission of a luminal osmotic stimulus. Additional ongoing studies are being conducted in dogs assessing the effects of the renin-angiotensin system on glomerular hemodynamics. In sodium-restricted dogs, at reduced renal arterial blood pressures, administration of captopril produces vasodilation of both afferent and efferent vessels and increases in single nephron and whole kidney GFR. The glomerular ultra-filtration coefficient (Kf) is not altered during blockade of angiotensin II formation. Captopril also produced increases in urine flow and sodium excretion. Future studies will be conducted to assess the role of the prostaglandins in mediating the hemodynamic and excretory responses found during captopril administration.